The introduction of drugs and chemical agents into living cells has recently begun to utilize nano-scale objects of less than 100 nanometer dimensions and/or microscopic objects, herein known as the subject particle, in various configurations as carriers. For example, therapeutic drugs can be coated onto, or encased within, nano-sized particles such as gold and silver. The functionalized subject particle is then introduced into the body, where it is absorbed into tissues and ultimately taken up by cells. The ability to target just the cells that should receive the drug is enabled by functional coatings on the particles, which are recognized by the cell surface. Research into the process of cell uptake of subject particles, and the intracellular processing of the drug-particle, is important for development of the drug therapy process. The cell-subject particle interactions that are involved in uptake and distribution within cells are elucidated by many different types of studies using diverse techniques.
One of the most widely used tools is cell imaging by fluorescent microscopy. Conventional fluorescent microscopy does not allow the three dimensional volume of the cell to be viewed. A confocal fluorescence microscope is therefore used to image thin sections of the cell over a volume to view the cell structure in three dimensions. However these methods require introduction of fluorescent labels. The attachment of fluorophores to subject particles or cell structures can alter the intended function for drug delivery and significantly increases the difficulty of the cell preparation. Systems and methods that permit determination of the location of subject particles in three dimensions without altering the intended function for drug delivery are therefore of interest and have the potential to play an important role in increasing the understanding of nano-drug delivery, thus furthering the development of nanomedicine.